Farmers use many agrochemicals to protect or improve their crops. Herbicides are the biologically active ingredients commonly used to control weeds or undesired vegetation in agriculture.
Glyphosate, N-(phosphonomethyl)-glycine, is one of the most frequently applied herbicides for non-selective control of weeds. It is present in a well-known commercial composition known mainly under the registered trademark ROUNDUP® sold by Monsanto but is also sold under many other trademarks by many other companies.
Glyphosate is a broad spectrum, post emergence herbicide commonly used in the domestic, industrial and agricultural markets for weed control.
Glyphosate is well known in the art as an effective herbicide and is by far the main pesticide applied worldwide. It is used on nearly all crops against approximately 300 different types of weeds. Glyphosate represents in value approximately 15% of the entire pesticide market.
Glyphosate may be formulated in a wide variety of liquid and solid compositions designed to cover a range of applications. Liquid formulations are by far the most common, because they can include liquid surfactants, which are less expensive than solid surfactants and can be incorporated directly into the glyphosate liquid formulations. Currently, liquid fatty amine ethoxylated derivatives are the main liquid surfactants used for glyphosate, but they are known for their toxicity.
Solid formulations have an advantage over liquid formulations in so far as they can present a higher concentration of the glyphosate active ingredient which increases their advantage over liquid formulations regarding the amount of product to be transported and therefore packing, freight, handling and storage costs. In addition, only using a solid formulation is it possible to prepare the glyphosate soluble salt in situ in the water tank. Consequently, researchers tend to favor the development of new glyphosate formulations in the form of a granule or powder.
The manufacture of a powder requires much less investment than that of a granule. There are, therefore, strong reasons for developing a formulation in the form of a powder
All herbicide formulations include a surfactant to lower surface tension and spread the pesticide on the leaf. Usually, solid formulations use solid surfactants which can be incorporated directly into a powder or granule. Most of these solid surfactants are much more expensive and less efficient with glyphosate than the liquid fatty amine derivatives currently used in most glyphosate liquid formulations.
One of the objectives of this invention was to be able to incorporate a highly efficient liquid surfactant, which has a low toxicity, is inexpensive, and is fully compatible and appropriate for use with the other components of the formulation, all in a readied in situ powder formulation. However the incorporation of a liquid surfactant in a readied in situ powder formulation is not a simple procedure. Therefore, the exclusion of these solid surfactants created an obstacle to the development of the powder formulation.
So, according to the instant invention, the presentation form for the composition as a readied in situ water soluble powder incorporating a highly efficient, low toxicity liquid surfactant, is an alternative to state of the art formulations and brings notable advantages, as one can see in the present description.
When glyphosate is applied to selected weeds it acts by interrupting protein formation, which is the basic component of living cells, thus killing the plant.
Protein synthesis in plants proceeds in three steps: (i) reduction of nitrates to nitrites followed by reduction of nitrites to ammonia (ii) formation of amino acids (iii) formation of proteins from amino acids via DNA/RNA replication.
Glyphosate acts in step (ii). A key reaction in the multi stage synthesis of the essential aromatic amino acids, phenylalanine and tryptophan, is the reaction between Shikimate-3-Phosphate and Phospho-Enol Pyruvate (PEP) to form a compound known as EPSP (5-enolpyruvylshikimate-3-phosphate). This reaction is catalyzed by an enzyme known as EPSPS (5-enolpyruvylshikimate-3-phosphate synthase). Glyphosate and PEP have a similar molecular structure so the fact that glyphosate mimics PEP leads EPSPS to take up glyphosate instead of PEP thereby inhibiting its action and interrupting the reaction sequence.
EPSPS does not present an accentuated preference for glyphosate or PEP so that the success of glyphosate is achieved by the sheer number of molecules of glyphosate which must crowd out a smaller number of molecules of PEP. Therefore it is vital to get the largest amount of glyphosate into the leaf in the shortest possible time. While this is an important consideration for all herbicides, it is particularly so for glyphosate the effective action of which depends exclusively upon the amount of product introduced into the leaf. If more glyphosate is made to enter the plant in a shorter time one can reduce the amount of glyphosate applied on the field.
In order to kill the plant, glyphosate must first get through the leaf cuticle which covers both sides of the leaf. Resistance to diffusion of the pesticide through the cuticle is due to an outer layer of wax as well as to waxes embedded in the cuticle itself.
The purpose of the cuticle is to avoid loss of water which would lead to desiccation of the plant. Since the cuticle avoids water from getting out, it also avoids water and therefore water soluble pesticides from getting in.
There is a growing trend to combine herbicides with adjuvants which increase the efficacy of the herbicide. The spray mixture for herbicide application contains an effective amount of known herbicide along with adjuvants and water. Sometimes the adjuvant must be added to ensure optimum performance of the actives in a variety of conditions which may otherwise inhibit it, for example, hard water, high temperatures, and poor growing conditions. The adjuvants, generally, are added to the herbicide spray mixture to enhance post emergence weed control and/or to reduce spray drift during herbicide application.
The types of substances which are used as adjuvant include plants nutrients, particularly, ammonium salts, wetting agents, spray drifts retardants, lipophilic solvents, surfactants and emulsifiers
Typically, the addition of ammonium ions by the introduction of an ammonium salt in the composition enhances the effect of glyphosate, possibly by accelerating the rate of diffusion through the cuticle.
Glyphosate is a highly polar structure. Because of the low dissociation constant (pKa=0.8) one of the protons of the acid migrates readily to the nitrogen atom leaving a negative charge on the phosphonic acid and a positive charge on the nitrogen atom, thus forming the zwitterion, which is described by the equation:COOHCH2NHCH2PO⇄COOHCH2NH2+CH2PO(OH)O−
Hydrophilic ions such as the zwitterion have difficulty diffusing through waxes and their rate of diffusion is much lower than for a non-dissociated molecule.
The addition of ammonium ions in the formulation by the introduction of an ammonium salt such as for instance ammonium sulfate leads to a less dissociated compound and consequently to a faster rate of diffusion. This faster rate of diffusion signifies that more glyphosate enters the plant in a shorter period of time which leads to a reduction in the amount of glyphosate required on the field,
Because of this effect, ammonium sulfate is often referred to as being an activator for glyphosate. Since ammonium sulfate is an inexpensive fertilizer, the combined exposure of weeds to this fertilizer and glyphosate can substantially increase the efficacy of the active molecule at a very low cost.
Considering that ammonium ions facilitate diffusion through the cuticle leading to a much faster rate of entry of glyphosate into the plant; and that there exists a specific necessary amount of glyphosate required to inhibit EPSPS, the researches of the instant invention surprisingly discovered that there exists a specific proportion of ammonium ions to glyphosate acid which leads to a maximum efficacy of the formulation supplied from a solution containing less glyphosate. So, according to the present application, despite the fact that many glyphosate herbicides use an ammonium salt as activator, only the determination of the optimum amount—defined as being the smallest amount of ammonium salt which leads to the maximum gain of efficacy—opens the possibility of designing a solid powder formulation with a very narrow amount of specific ingredients of composition so as to present simultaneously all the desired properties of greatly increased efficacy, in situ preparation of the soluble glyphosate salt in the water tank, and a high content of the glyphosate active ingredient.
One can conclude that the faster rate of glyphosate diffusion through the leaf cuticle occurs in herbicide formulations which contain ammonium ions, and that, this faster rate of diffusion leads to a reduction in the amount of glyphosate required on the field, in order to produce the improved results. One can further conclude from the zwitterion dissociation equilibrium that there is an optimum amount of ammonium ions to be used in order to minimize dissociation of the glyphosate molecule.
Any inorganic salt which acts as a supplier of ammonium ions can be used, such as, ammonium nitrate, ammonium chloride, ammonium carbonate, ammonium bicarbonate, ammonium phosphate or ammonium sulfate. Ammonium nitrate is less attractive being commonly used as an oxidizing agent in explosives. Also it requires the use of more product per ammonium ion. Ammonium chloride is more expensive than ammonium sulfate and has the disadvantage that the chloride ion will presumably end up as sodium chloride and it is undesirable to salt the soil. Ammonium carbonate is much more expensive than the other salts. For these reasons the applicant of the present invention selected ammonium sulfate as the preferable activator. Ammonium phosphate is a valid alternative.
Ammonium sulfate's main use is as an inexpensive fertilizer. The combined exposure of weeds to this fertilizer and glyphosate can substantially increase the efficacy of glyphosate. This fertilizer accelerates the translocation of the glyphosate herbicide within the weeds, increasing the kill rate of the weeds. The use of an inexpensive fertilizer can increase the efficacy of glyphosate at a minimum cost. However, the use of ammonium sulfate is problematic because its solubility in water varies with changes in water quality. Water temperatures, hardness and mineral content all affect the mixing of ammonium sulfate in the spray mixture. This unpredictable solubility has been problematic for farmers who need to apply glyphosate to kill weeds in a crop.
Therefore typically, commercial glyphosate formulations contain an adjuvant surfactant to provide increased spray retention on the leaf surface and increase herbicide absorption into the plant. However, a surfactant alone often is not able to increase herbicide efficacy, especially when hard or very hard water is used as a spray carrier.
In addition, the surfactant in commercial glyphosate formulations is often not sufficient to optimize efficacy and does not prevent antagonism from spray-carrier cations. Thus, a combination of a surfactant and ammonium salts is required. Ammonium sulfate overcomes the antagonistic effect of sodium, calcium and magnesium ions in hard water. Furthermore, ammonium ions from an ammonium salt such as ammonium sulfate, provided that they are present in an adequate amount, greatly increase glyphosate herbicide absorption. The mixture of an appropriate surfactant and ammonium sulfate is a beneficial combination that increases the efficacy of many herbicides, particularly glyphosate.
Most surfactant adjuvants sold for use with herbicides are physically compatible with ammonium sulfate when diluted with water in a sprayer tank. However, specific surfactants are required for maximum efficacy when used in combination with ammonium sulfate and the choice of the wrong surfactant can reduce efficacy. Thus the effect of ammonium sulfate is markedly dependent on the type of surfactant. There are a large number of surfactant products available, so it is difficult to establish which is the most effective compound to be used with ammonium sulfate.
The preferential formulation is understood as one which could attend to all the commercial and environmental requirements, such as, maximum reduction in glyphosate amount associated with the highest activity, low toxicity and cost effectiveness. For solid formulations, researchers have used mainly solid surfactants which are easily incorporated in a powder or granule but are generally more expensive and less efficient than liquid fatty amine derivatives commonly used in glyphosate liquid formulations so that until now, they did not find the ideal surfactant for a glyphosate powder formulation containing ammonium sulfate.
There are two pathways for the glyphosate penetration into the plant leaf, either through the stomata or by diffusion through the outer layer of wax which covers the cuticle and through the cuticle itself.
Entry through the stomata can only occur during the short period of time that follows the application of the formulation and while there is still a liquid on the surface of the leaf, that is, before evaporation of the solvent. Furthermore, surface tension is usually not low enough to allow for penetration through the stomata. Therefore, by far the main route for entry and translocation of glyphosate is by diffusion. The main resistance to diffusion is the waxes embedded in the cuticular layer, and to a lesser degree the wax crystals and wax film embedded in the cuticle. So, these conditions represent the main technical features that researchers have to overcome in order to develop ideal herbicidal compositions.
According to U.S. Pat. No. 5,591,443, amide surfactants are described as suitable membrane transfer agents. Said patent discloses a proteinaceous insecticidal composition for combating insects. The composition consists of a synergistic combination of a unique type of protein prepared from casein with an effective critical amount of this membrane transfer agent that will translocate this unique protein across normally impermeable membrane barriers. Preferred membrane transfer agents are N-monoalkanolamine or N-dialkanolamine fatty acid amide and N-propylbetaine fatty acid amide.
It should be observed that this type of surfactant is used in order to transfer proteinaceous extracts across normally impermeable insect membranes. Moreover, the U.S. Pat. No. 5,591,443 patent does not intend to kill weeds nor to develop a single readied in situ soluble powder glyphosate herbicide formulation characterized by a very narrow amount of a specific ingredients of composition, which optimize formulation efficiency, minimize costs and toxicity.
So, considering the remarkable effect of the surfactant agent with ammonium sulfate present in the applicant invention, one cannot consider obvious the choice of these substances to act as a surfactant suitable for the improved herbicide powder composition.
According to EP 498.145, a solid phytoactive glyphosate composition is provided. The solid composition comprises: (a) N-phosphonomethylglycine in the form of a salt or the free acid; (b) a surfactant comprising an alkyl glycoside or alkyl polyglycoside; and, (c) an agriculturally acceptable inorganic ammonium salt, preferably ammonium sulfate which is used to increase the efficacy of the formulation.
However, it should be observed that EP 498.145 discloses a granulate composition and not a powder composition as the present invention does.
According to the description of the reference, the process for preparing the granular composition comprises reacting an acid acceptor with glyphosate or using glyphosate directly; mixing the solid alkyl glucoside or alkyl polyglucoside and ammonium sulfate in order to prepare a pasty mixture and thereafter granulating, extruding or spray drying to prepare said solid composition. On the other hand, the present application discloses a powder formulation which is not submitted to a granulation process. Besides, said patent does not try to optimize the ratio of ammonium sulfate to glyphosate acid as the present invention. This is illustrated by the use of an ammonium sulfate concentration from 20% to 80%. A concentration of 20% in the formulation is below the optimal and more than 30% serves no useful purpose. Without optimization of the ammonium sulfate to glyphosate ratio one cannot have in situ preparation of the soluble glyphosate salt nor maximize the concentration of glyphosate in the formulation.
Consequently the patent does not describe in situ production, while the present invention discloses one and the concentrations of glyphosate acid active ingredient described in said patent are much lower than the concentrations achieved in the present invention. Moreover, the surfactant adjuvant judiciously selected by the applicant is not a substance derived from glycoside or polyglycoside.
Actually, according to the present invention, the suitable surfactants specially selected for high efficiency, low toxicity as well as to act as an agglomerating agent for herbicide powder particles are liquid fatty acid amide derivatives which have high efficiency, low toxicity and are inexpensive.
U.S. Pat. No. 6,228,807 discloses a dry water-soluble agricultural acceptable herbicidal composition, which can be prepared as a water soluble powder form comprising N-phosphonomethylglycine or a water soluble salt of N-phosphonomethylglycine. It describes the use of at least one surfactant which in its form is liquid at 25° C. Actually it describes the use of any liquid surfactants, such as, nonionic, anionic, cationic and amphoteric ones. The surfactant gels in water and enhances the bioefficacy having less than about 5% by weight of water.
According to this document, the salt is prepared by a separate operation and not in situ in the water tank. The purpose of the invention is not related to obtaining a reduction of the amount of glyphosate active ingredient to be applied on the field by an increase in efficacy of the formulation. Ammonium sulfate is mentioned as an adjuvant, but there is no indication of ammonium sulfate being used to increase the efficacy of the formulation, because this is not the purpose of the patent. Consequently the amount of ammonium sulfate required in order to obtain an increase in efficacy is not mentioned nor is there any indication of an optimum ratio of ammonium sulfate to glyphosate acid which leads to a 30% increase in efficacy in the field. An increased efficacy is not sought after since this is not the objective of the U.S. Pat. No. 6,228,807 patent or a researched result. The herbicide composition contains any type of surfactant. This means that this US patent does not aim to improve its composition by choosing a specific surfactant. The document does not mention a judicious selection of a surfactant adjuvant. Ethoxylated coco amine is mentioned in the description but this is completely different from the surfactants used in the present application which specifically excludes the use of this compound because of its toxicity. Thus the product described in the patent is more toxic than the formulation of the present invention and the higher efficacy is not sought after since this is not the object of the patent.
WO 2010/053385 A1 discloses a liquid, homogeneous composition comprising a water-soluble glyphosate salt and a mixture of adjuvants including at least one surfactant, ammonium sulfate, at least one carboxylic acid preferably citric acid and a mixture of compatibilising substances preferably glycol and triethanolamine. While the purpose of the invention is to increase the efficacy of glyphosate, no reference is made to optimization of the ratio of ammonium sulfate to glyphosate and the suggested concentration of ammonium sulfate is twice the amount required by the present invention. The formulation described in this patent is entirely different from the composition object of the present invention, being a liquid instead of a powder, and using a water soluble salt instead of glyphosate acid.
The liquid form creates the need to add the carboxylic acid in addition to the two compatibilising substances in order to stabilize the formulation while the powder formulation does not require the addition of any of these three substances.
The liquid composition also requires the prior preparation of the glyphosate salt by a separate operation which increases the cost of the formulation, while for the powder formulation described in the present invention this is not required since the glyphosate salt is prepared in situ in the water tank. Furthermore because of the limited solubility of ammonium sulfate in water the use of a liquid formulation limits the concentration of the glyphosate active ingredient in the formulation to a value well below—approximately half—of that which is achieved with a powder.
U.S. Pat. No. 5,118,338 refers to a water soluble powder or granular free flowing glyphosate formulation and a surfactant that is a powdery or granular non-ionic polyglycol ether of a straight chain, saturated, high molecular weight fatty alcohol having an average chain length of C16-C18, about 25 units of ethylene oxide per mole of fatty alcohol and an HLB value of about 16. Suitable penetrating agents, such as, ammonium sulfate can be used. The patent envisages exclusively the use of a solid surfactant while the present invention envisages only liquid surfactants which are less expensive, less toxic and more efficient.
The patent uses polyglycol ethers that are produced by ethoxylation and therefore contain 1,4-dioxane which is a carcinogen while the present invention rejects this type of surfactant. In addition, the patent discloses the use of other additives in the form of liquids that may be added in minor amounts as long as they do not change the physical free flowing character of the formulation.
Thus, according to the patent referenced above, ammonium sulfate is one of the possible additives that can be included into the formulation, while in the present invention, ammonium sulfate is a critical ingredient, the new herbicide composition of the present invention being characterized by a judicious selection and a very narrow range concentration of its components.
The solid polyglycol ether is simple to incorporate in a powder formulation while the specific liquid surfactant that is used in the product of the instant invention is far more difficult to incorporate in a powder formulation. Moreover, the surfactant adjuvant judiciously selected by the applicant of the present invention is not a substance derived from polyglycol ether.
While ammonium sulfate is contemplated as an adjuvant for increase of efficacy, the optimum ratio of ammonium sulfate to glyphosate is not an object of the research and the concentration of ammonium sulfate is much higher than required. The consequence is that in situ preparation of the soluble glyphosate salt of the reference patent is not possible, since no space is left in the formulation for a solubility agent in order to form the soluble glyphosate salt in situ in the water tank.